1. Field of Invention
The present invention relates to a method of screening or diagnosis which makes it possible to detect the presence of a prostate cancer or of a benign prostate hyperplasia (BPH) in a patient, this being without performing a biopsy.
2. Description of Related Art
Indeed, the prostate specific antigen, more commonly called PSA, is the principal marker for prostate cancer which will affect, during one's life, one man out of six in the West. This protease of the kallikrein family, mainly secreted by the prostatic epithelium, is found at a concentration of 0.5 to 5 mg/ml in the seminal fluid and at a concentration one million times lower in the serum of a patient. This serum PSA level increases markedly during a prostate cancer and moderately during benign impairments, such as BPH, acute prostatitis, and the like.
However, the area of overlap between the various pathologies is responsible for a substantial lack of sensitivity and of specificity. Accordingly, 30 to 45%of cancers confined to the gland, which constitutes an early and potentially curable stage, are not detected with the usual threshold of 4 ng/ml whereas three patients out of four are wrongly suspected.
In addition, it has recently been shown that in serum, PSA combined with protease inhibitors such as α-1-antichymostrypsin (ACT), and that the use of the free PSA to total PSA ratio made it possible to improve the specificity of the diagnosis.
The prior art therefore shows that techniques exist which make it possible to diagnose the development of a prostate cancer in patients. Thus, patent application WO-A-97/12245 claims a method which makes it possible to diagnose an adenocarcinoma of the prostate (CAP) without biopsy. This method consists in measuring, in the serum or in the blood of patients, the total quantity of PSA. If this value is between 2.5 and 20 ng/ml, the concentration of free PSA is also measured. The free PSA to total PSA ratio is then calculated. If this ratio is less than 7%, the diagnosis is oriented toward an adenocarcinoma of the prostate.
However, the use of a 7% threshold for the diagnosis of a cancer of the prostate is much debated by many authors, as shown by the publication by Lein et al. “Relation of free PSA/total PSA in serum for differentiating between patients with prostatic cancer and benign prostate hyperplasia: which cutoff should be used?”. In this document published in the journal Cancer Investigation, 16(1), 45-49, 1998, it has been shown that it is difficult to systematically differentiate a cancer or adenocarcinoma of the prostate from a BPH by means of this ratio.
In addition, the publication by Catalona et al., “Prostate Cancer Detection in Men With Serum PSA Concentrations of 2.6 to 4.0 ng/ml and Benign Prostate Examination”, published in JAMA of 14 May 1997-Vol. 277, No. 18, demonstrates a concentration less than 4 ng/ml should be taken into consideration in order to make an early diagnosis of a cancer of the prostate.
Moreover, in the seminal fluid, PSA may have internal cleavage sites which do not affect its three-dimensional cohesion because of the existence of five disulfide bridges which link the various fragments of the molecule. The PSA thus cleaved loses its enzymatic activity and its capacity to bind to protease inhibitors. However, in the serum, no cleaved form is generally mentioned in the prior state of the art.
No cleaved form has so far been reported in cases of benign pathologies of the prostate and the value of the cleaved forms has not been explored for diagnostic purposes.